Dosage forms conventionally used for the formulation of light-unstable substances include coated tablets, hard capsules, soft capsules, as well as oral solutions and powders filled in light-shielding containers. For example, JP 5-15691 B reports an example of soft capsule formulation whose shell is supplemented with 0.2 wt % of titanium oxide. Also, JP 57-4345 B reports an example of hard capsule formulation which contains 2 wt % or less of titanium oxide in combination with 0.5 wt % or less of iron oxide red. In certain cases such as where light-unstable substances are in a liquid form (e.g., oils, suspensions, emulsions) or are hardly soluble or easily oxidizable, dosage forms preferably used are soft capsules having a light-shielding shell.
Techniques known for manufacturing soft capsules include the plate method or the rotary method in which two sheet materials for shell formation are punched and shaped into capsules, as well as the in-liquid curing coating method (drop method) in which a solution to be encapsulated and a shell-forming solution are simultaneously dripped into a curing solution through a double nozzle. Soft capsules manufactured by the in-liquid curing coating method are also called seamless soft capsules because of their seamless shell.
When compared to the plate method and the rotary method, the in-liquid curing coating method enables the manufacture of soft capsule formulations having a smaller capsule size (e.g., 2 mm or less), thus also enabling the manufacture of granular soft capsule formulations which are readily taken by children, elderly people, or patients with reduced swallowing ability. Such formulations of smaller size are expected to have improved dispersibility of medicaments in the digestive tract and reduced variations in medicament absorption.
Commonly used soft capsule formulations have a capsule size of about 4 to 20 mm and a shell thickness of about 200 to 600 μm. It is therefore possible to achieve effective light shielding of the encapsulated active ingredient(s) when the shell is supplemented with about 0.1 to 2 wt % of a light-shielding agent, as stated above. However, in conventional techniques, it was inevitable that the shell thickness would be reduced as the capsule size decreased. For this reason, in the case of soft capsule formulations having a capsule size of 2 mm or less, conventional recipes for capsule shell could not ensure a shell thickness enough to provide sufficient light shielding of a light-unstable active ingredient.
As stated above, no soft capsule formulation has been developed for commercial use, which has a small capsule size and sufficiently prevents photodegradation of the encapsulated medicament by the action of a light-shielding shell.